DreamRCT: The PANIC Trial

Contrast nephropathy: Is it real?

If you had unlimited resources, what nephrology clinical trial would you conduct? That's the big idea behind DreamRCT, a project of UKidney created by Joel Topf, MD, and Jordan Weinstein, MD, in partnership with MedPage Today. Vote for your favorite trial at UKidney.com.

Contrast-induced acute kidney injury (CI-AKI) is a widely recognized phenomenon. But in recent times, there has been a question as to whether it even truly exists in relation to modern IV contrast used for CT imaging. The evidence for a causal relationship is remarkably scarce and consists largely of observational studies and meta-analyses, and while this has led to ongoing debate as to the existence of CI-AKI, common clinical practice behaves as though it is a definite recognized entity.

AKI for any reason is associated with increased mortality, and while this may be a causal relationship or in certain cases more a reflection of baseline co-morbidities, we certainly want to avoid AKI wherever possible. That said, the fear of CI-AKI may cause clinicians to avoid IV contrast in situations where its use may lead to more timely diagnosis, more effective care, and ultimately decreased overall mortality -- with or without AKI. The consideration of CI-AKI impacts decisions on a daily basis in hospitals. If a patient has any renal insufficiency -- whether acute or chronic -- the tendency is to avoid contrast, either by getting a noncontrast CT (which is usually diagnostically inferior for patients in whom contrast enhanced imaging is the initial test of choice) or by avoiding CT altogether, where the presumption is that noncontrast CT would likely be too nondiagnostic to be of any management value. A clinician may even choose to delay a contrast study in order to allow time for "prehydration" or other tactics to reduce the risk of CI-AKI.

Prior studies that focused on quantifying the incidence of CI-AKI have shown conflicting results. Two more recent studies have often been cited; the first by Davenport et al looked at 20,242 CT scans and concluded that contrast administration was an independent risk factor for AKI in patients with pre-administration creatinine > 1.6 mg/dL. Their definition of AKI was an increase in serum creatinine of 50% over baseline or an increase of 0.3 mg/dL or more (KDOQI AKI Stage 1). Another study was a large meta-analysis in 2013 by McDonald et al, which found no significant difference in the incidence of AKI, dialysis, and death in contrast-exposed and non-exposed groups. To date, there have been no randomized trials that link IV contrast and AKI in a causal manner. However, in the analyses of the large bodies of observational data to date, it would appear CI-AKI is a rarer phenomenon that is appreciated -- if it exists at all.

The DreamRCT I propose -- Prospective Assessment of Nephropathy due to Intravenous Contrast: a Randomized Controlled (PANIC) Trial -- would aim to describe the true incidence of contrast nephropathy. The inclusion criteria would be populations who are classically at risk for CI-AKI: those with pre-existing chronic kidney disease stage 3b-4. If CI-AKI exists, this is where it will be found. I would enroll subjects at their baseline state of health. One would be hard pressed to randomize patients to contrast or no contrast in the acute setting where contrast is needed to make critical diagnostic and management decisions.

Subjects would be randomized to receiving IV contrast and not receiving IV contrast. No scan need be done. Serum creatinine would be measured pre-exposure and daily for up to one week post-exposure. In this setting, a rise in creatinine is also far less likely to be due to alternative explanations for AKI, which are numerous in hospitalized patients. It would be fair to continue to use the laboratory definition of AKI of >1.5-fold increase or >0.3 mg/dL increase in serum creatinine. While this can lead to greater spurious diagnosis of AKI at higher baseline creatinine levels, the effect should be comparable across both trial arms.

This trial would be a first step. It does not, however, replicate the clinical scenario where patients are getting contrast enhanced CT scans for diagnostic purposes in the setting of an acute illness, the nature of which is frequently uncertain. But if we show in a randomized controlled trial that IV contrast has no nephrotoxic potential in otherwise healthy CKD patients, then it can pave the way for more definitive, clinically convincing studies that answer tough clinical questions. Does the morbidity/mortality from possible nephropathy outweigh the morbidity/mortality that comes from delayed or missed diagnosis? Is post-contrast AKI "just a number" or does it have real implications for morbidity/mortality? Is it possible for a contrast CT to "push" an advanced CKD patient into needing dialysis? Is it possible for a contrast CT to obliterate the remaining renal function of dialysis patients who still make urine?

It's amazing that for so long we've not had an RCT answering the most basic question -- is there such a thing as contrast nephropathy? And even if the answer is yes, then the next question is, what does it all mean? Ultimately, the bottom line has to do with the safety of IV contrast, weighed against the risk of delayed or missed diagnosis. Of the two, the first is the more straightforward component to pursue; the latter is extremely variable and it would be impossible to design feasible trials without first having a better understanding of the true risk of IV contrast.

So there you have it. Contrast nephropathy... is it real, or just a #DreamRCT?

Chi Chu, MD, (@cdchu) is an internal medicine resident at California Pacific Medical Center in San Francisco. His interests include nephrology, patient safety, and medical education.

Accessibility Statement

At MedPage Today, we are committed to ensuring that individuals with disabilities can access all of the content offered by MedPage Today through our website and other properties. If you are having trouble accessing www.medpagetoday.com, MedPageToday's mobile apps, please email legal@ziffdavis.com for assistance. Please put "ADA Inquiry" in the subject line of your email.